title: General oxidative stress during doxorubicin-induced cardiotoxicity in rats: absence of cardioprotection and low antioxidant efficiency of alpha-lipoic acid.
abstract: To evaluate the effects of alpha-lipoic acid (AL) in a model of doxorubicin (DOX)-induced cardiotoxicity, male Wistar rats were treated with DOX (1 mg/kg/d; 10 d) in combination or not with AL (50 mg/kg/d; 15 d). Plasma oxidative stress was determined by hydroperoxides (ROOH) and the ascorbyl radical/ascorbate ratio. One and two months later, the functional parameters of the hearts were determined in vivo by catheterization and cardiac oxidative stress was assessed by malonedialdehyde (MDA) and O₂*⁻ (dihydroethidium fluorescence) content in tissue. After two months, body weight was higher in the DOX-AL group than in DOX (+16%), but this was due to ascites. Histological liver alterations were observed in both the DOX and DOX-AL groups. Plasma ROOH concentrations decreased after 10 days of AL treatment, but were greater in both the DOX and DOX-AL groups. After two months, a decrease in the cardiac contractility index (-27% and -29%, respectively) and cardiac hypertrophy were observed in DOX and DOX-AL. These dysfunctions were associated with 1) a reduction in plasma ascorbate levels and an increase in the ascorbyl/ascorbate ratio and 2) an increase MDA and O₂*⁻ content in cardiac tissue. In conclusion, a cumulative dose of 10 mg/kg doxorubicin induced functional alterations in the heart associated with plasma and cardiac oxidative stress. The co-administration of the antioxidant compound AL had no beneficial effects in this situation.
authors.affiliation: Department of Pharmacology, Physiology and Physiopathology, Faculty of Pharmacy, University of Medicine and Pharmacy, Cluj-Napoca, Romania.
authors.forename: Steliana
authors.initials: S
authors.lastname: Ghibu
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Delemasure
authors.forename: Carole
authors.initials: C
authors.lastname: Richard
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Guilland
authors.forename: Laurent
authors.initials: L
authors.lastname: Martin
authors.forename: Ségolène
authors.initials: S
authors.lastname: Gambert
authors.forename: Luc
authors.initials: L
authors.lastname: Rochette
authors.forename: Catherine
authors.initials: C
authors.lastname: Vergely
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D001202:Ascitic Fluid / Q000473:pathology; D001205:Ascorbic Acid / Q000097:blood; D001835:Body Weight / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D054715:Cardiotoxins / Q000633:toxicity*; D004317:Doxorubicin / Q000633:toxicity*; D004435:Eating; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006331:Heart Diseases / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control*; D006400:Hematocrit; D006861:Hydrogen Peroxide / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D013481:Superoxides / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D008063:Thioctic Acid / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000903:Antibiotics, Antineoplastic; D000975:Antioxidants; D002316:Cardiotonic Agents; D054715:Cardiotoxins; D017392:Thiobarbituric Acid Reactive Substances; D013481:Superoxides; D008063:Thioctic Acid; D004317:Doxorubicin; D006861:Hydrogen Peroxide; D001205:Ascorbic Acid